Michel De Pauw

Iron deficiency is associated with adverse outcome in Eisenmenger patients.

AIMS Iron deficiency is common in patients with Eisenmenger syndrome (ES). This study aimed at evaluating (i) whether iron deficiency is related with adverse outcome, (ii) the determinants of iron deficiency, and (iii) the relation between iron reserves and haemoglobin level in a contemporary cohort of ES patients. METHODS AND RESULTS All ES patients, older than 18 years, selected from the Belgian Eisenmenger registry, were prospectively followed using a web-based registry. Univariate Cox-regression analysis was performed to evaluate the relation with outcome, defined as all-cause mortality, transplantation, and hospitalisation due to cardiopulmonary causes. Bivariate analysis was performed where applicable. A total of 68 patients with a complete dataset (mean age 36.9 ± 14.2 years; 30.9% male) were included. During a median follow-up time of 3.1 years, 21 patients (30.9%) reached the predefined endpoint. New York Heart Association (NYHA) class ≥ III (HR 4.76; 95% CI 1.84-12.30; P = 0.001), iron deficiency (HR 5.29; 95% CI 2.04-13.76; P = 0.001), mean corpuscular volume (MCV) (HR 0.94; 95% CI 0.90-0.99; P = 0.021), and mean corpuscular haemoglobin (MCH) (HR 0.87; 95% CI 0.76-0.98; P = 0.027) were related with adverse outcome. The use of oral anticoagulation and frequent phlebotomies were independently related with iron deficiency (P = 0.005 and P = 0.008). In iron-deplete patients, MCV (R = -0.408; P= 0.014) and MCH (R = -0.437; P = 0.026) were inversely related with haematocrit. In patients with low oxygen saturation, iron reserves were related with haemoglobin levels (R = 0.587; P = 0.001). CONCLUSIONS Iron deficiency was associated with a higher risk of adverse outcome. Moreover, the use of oral anticoagulation OAC and frequent phlebotomies were related to iron deficiency. Patients under anticoagulation should be monitored rigorously for iron deficiency. However, in patients with low oxygen saturations, careful iron substitution to avoid too high haemoglobin levels is suggested.

Preinfarction angina protects against out-of-hospital ventricular fibrillation in patients with acute occlusion of the left coronary artery

OBJECTIVES The goal of this study was to evaluate the effect of preconditioning on out-of-hospital ventricular fibrillation (VF) in patients with acute myocardial infarction (AMI). BACKGROUND More than half of the deaths associated with AMI occur out of the hospital and within 1 h of symptom onset. In humans, preinfarction angina (PA), which can serve as a surrogate marker for preconditioning, reduces infarct size, but the protective effect against out-of-hospital VF has not been investigated. METHODS Preinfarction angina status and acute coronary angiographic findings of 72 consecutive patients with AMI complicated by out-of-hospital VF were compared with 144 matched controls without this complication. RESULTS Preinfarction angina is associated with a lower risk for VF (odds ratio [OR]: 0.40, 95% confidence interval [CI]: 0.18 to 0.88). In patients with acute occlusion of the left coronary artery (LCA) (n = 136), the risk reduction is pronounced (OR: 0.25, 95% CI: 0.10 to 0.66), whereas, in patients with acute occlusion of the right coronary artery (RCA) (n = 67), the protective effect of PA on VF was not observed (OR: 2.25, 95% CI: 0.45 to 11.22). Subgroup and multivariate analyses show that the protective effect is independent of cardiovascular risk factors, preinfarction treatment with beta-adrenergic blocking agents or aspirin, the presence of collaterals or residual antegrade flow or the extent of coronary artery disease. CONCLUSIONS Preinfarction angina protects against out-of-hospital VF in patients with acute occlusion of the LCA. This protection is independent of risk factors or coronary anatomy. A larger study is needed to examine the apparently different effect in patients with acute occlusion of the RCA.

Acute and critically ill peripartum cardiomyopathy and 'bridge to' therapeutic options: a single center experience with intra-aortic balloon pump, extra corporeal membrane oxygenation and continuous-flow left ventricular assist devices

IntroductionPeripartum cardiomyopathy (PPCM) patients refractory to medical therapy and intra-aortic balloon pump (IABP) counterpulsation or in whom weaning from these therapies is impossible, are candidates for a left ventricular assist device (LVAD) as a bridge to recovery or transplant. Continuous-flow LVADs are smaller, have a better long-term durability and are associated with better outcomes. Extra corporeal membrane oxygenation (ECMO) can be used as a temporary support in patients with refractory cardiogenic shock. The aim of this study was to evaluate the efficacy and safety of mechanical support in acute and critically ill PPCM patients.MethodsThis was a retrospective search of the patient database of the Ghent University hospital (2000 to 2010).ResultsSix PPCM-patients were treated with mechanical support. Three patients presented in the postpartum period and three patients at the end of pregnancy. All were treated with IABP, the duration of IABP support ranged from 1 to 13 days. An ECMO was inserted in one patient who presented with cardiogenic shock, multiple organ dysfunction syndrome and a stillborn baby. Two patients showed partial recovery and could be weaned off the IABP. Four patients were implanted with a continuous-flow LVAD (HeartMate II®, Thoratec Inc.), including the ECMO-patient. Three LVAD patients were successfully transplanted 78, 126 and 360 days after LVAD implant; one patient is still on the transplant waiting list. We observed one peripheral thrombotic complication due to IABP and five early bleeding complications in three LVAD patients. One patient died suddenly two years after transplantation.ConclusionsIn PPCM with refractory heart failure IABP was safe and efficient as a bridge to recovery or as a bridge to LVAD. ECMO provided temporary support as a bridge to LVAD, while the newer continuous-flow LVADs offered a safe bridge to transplant.

Is it time for a cardiac allocation score? First results from the Eurotransplant pilot study on a survival benefit–based heart allocation

BACKGROUND Patients awaiting heart transplantation in Eurotransplant are prioritized by waiting time and medical urgency. To reduce mortality, the introduction of post-transplant survival in an allocation model based on the concept of survival benefit might be more appropriate. The aim of this study was to assess the prognostic accuracy of the heart failure survival score (HFSS), the Seattle heart failure model (SHFM), the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) model, and the index for mortality prediction after cardiac transplantation (IMPACT) score for predicting mortality. METHODS The HFSS, SHFM, the adapted SHFM, and the INTERMACS model were evaluated for predicting waiting list mortality among heart transplant candidates, and the IMPACT score was tested for predicting post-transplant mortality in separate Cox regression models. Included were the 448 adult heart transplant candidates listed for an urgent status between October 2010 and June 2011 in Eurotransplant. A cardiac allocation score (CAS) was calculated based on the estimated survival times as predicted by the scores. All analyses were performed for the total cohort and separately for ventricular assist device (VAD) and non-VAD patients. RESULTS Mortality on the waiting list could significantly be predicted in the non-VAD cohort by HFSS (p = 0.005) and SHFM (p < 0.0001) and after transplant by IMPACT (p < 0.0001). None of the tested scores could predict mortality among VAD-supported patients. CONCLUSIONS In non-VAD patients, the HFSS, SHFM, and IMPACT provide accurate risk stratification. Further studies will reveal whether these models should be considered as the basis for a new heart allocation policy in Eurotransplant.

The Belgian Eisenmenger syndrome registry : implications for treatment strategies?

Objective — Pulmonary arterial hypertension (PAH), associated with congenital heart disease (CHD), usually results from a systemic-to-pulmonary shunt. Eisenmenger syndrome (ES) is characterised by severe irreversible PAH and reversal of a previous systemic-to-pulmonary shunt.A national registry of ES patients was initiated to optimise patient care and to provide epidemiological information regarding PAH and CHD in Belgium. Methods — All ES patients, older than 18 years, were selected through the local databases of ten centres in Belgium.After written informed consent, demographic, clinical, biochemical, technical, and treatment data were entered into the web-based registry. Results — Ninety-one patients were included in the registry. Mean age was 36 ± 11 years (range 18-59 years). Complete atrioventricular septal defect (N = 26, 28.6%), followed by ventricular septal defect (N = 25, 27.5%) were the commonest defects. Forty-five percent were patients with Down syndrome. Down patients were younger (32 ± 9 versus 40 ± 12 years;P = 0.039), had worse functional capacity (class II/III ratio: 15/16 versus 21/8; P = 0.035) and received significantly less specific PAH treatment (7% versus 38%;P = 0.002). Conclusion — Through the national Eisenmenger registry, 91 adult patients with ES were identified (estimated prevalence 11 per million inhabitants). Almost half of them were Down patients. Although having worse functional capacity, significantly less Down patients were receiving specific PAH treatment.

Fibrinogen and C-reactive protein on admission as markers of final infarct size after primary angioplasty for acute myocardial infarction

BACKGROUND In acute myocardial infarction (AMI) treated conservatively or with thrombolysis, marked increases of C-reactive protein (CRP) and fibrinogen have been observed. No data are however available concerning a possible relation between CRP and fibrinogen levels on admission and markers of infarct size after obtaining thrombolysis in myocardial infarction (TIMI) flow III by primary angioplasty. METHODS We studied 34 patients with a first AMI (29 men, mean age 54+/-11 years) who were treated with primary angioplasty (TIMI flow III in all patients, no concomitant treatment with glycoprotein IIb-IIIa antagonists) within 6 h of onset of pain. CRP and fibrinogen levels on admission were determined and related to the following markers of infarct size: peak creatine kinase MB (CKMB) levels, radionuclide left ventricular ejection fraction (LVEF) at discharge and thallium-201 single-photon emission computed tomography (SPECT) infarct size at 1 month. RESULTS Median CRP levels were 0.4 mg/dl (range 0.09-3 mg/dl), median fibrinogen levels 412 mg/dl (range 198-679 mg/dl), mean CKMB was 178+/-151 U/l, mean LVEF 52+/-8% and mean thallium-201 infarct size 7+/-6%. Although CRP levels were related to fibrinogen levels on admission (r=0.56, P=0.002), only fibrinogen levels were related to markers of infarct size (r=0.58, P=0.001 for CKMB, r=-0.44, P=0.01 for LVEF and r=0.64, P=0.001 for thallium-201 infarct size). No relation was found between CRP or fibrinogen levels on admission and the extent of coronary artery disease or the myocardial area at risk. In multiple regression analysis, the relation between fibrinogen and markers of infarct size was independent of CRP levels and the duration of pain on admission. CONCLUSIONS These findings indicate a relation between fibrinogen levels on admission and myocardial infarct size in patients treated with primary angioplasty for AMI. This relation seems to be independent of CRP levels and the duration of pain on admission. If confirmed in larger patient populations, fibrinogen levels on admission could have an important value for risk stratification and more aggressive reduction of infarct size in patients who are treated with primary angioplasty.

Echocardiography for the detection of portopulmonary hypertension in liver transplant candidates: An analysis of cutoff values

Portopulmonary hypertension (POPH), a complication of chronic liver disease, may be a contraindication to liver transplantation (LT) because of the elevated risk of peritransplant and posttransplant morbidity and mortality. Because POPH is frequently asymptomatic, screening with echocardiography is recommended. The only reliable technique, however, for diagnosing POPH is right heart catheterization (RHC). The aims of this study were to evaluate the current estimated systolic pulmonary artery pressure (sPAP) cutoff value of 30 mm Hg and to determine a better cutoff value. One hundred fifty‐two patients underwent pretransplant echocardiography between January 2005 and December 2010. These echocardiographic results were compared with pulmonary artery pressures measured during the pretransplant workup or at the beginning of the transplantation procedure (both by catheterization). With a cutoff value of 30 mm Hg, 74 of the 152 patients met the criteria for POPH on echocardiography, although the diagnosis was confirmed in only 7 patients during catheterization; this resulted in a specificity of 54%. It would have been more accurate to use a cutoff value of 38 mm Hg, which had a maximal specificity of 82% and, at the same time, guaranteed a sensitivity and negative predictive value of 100%. With the incorporation of the presence or absence of right ventricular dilatation, the specificity even increased to 93% for this new cutoff value. In conclusion, the prevalence of POPH was 4.6% among LT candidates in this study. We can recommend that LT candidates with an sPAP > 38 mm Hg should be referred for RHC. With the cutoff value increased from 30 to 38 mm Hg, the number of patients undergoing invasive RHC during their evaluation could be safely reduced. Liver Transpl 19:602–610, 2013.

Oral vasodilator therapy in patients with moderate to severe portopulmonary hypertension as a bridge to liver transplantation

Portopulmonary hypertension (POPH) is a part of group 1 pulmonary hypertension (pulmonary hypertension associated with portal hypertension). Liver transplantation (LTx) may be curative, but is usually restricted to patients with mild-to-moderate POPH. The presence of severe POPH may be a contraindication to transplantation because of the elevated risk of peritransplantation and post-transplantation morbidity and mortality. This report describes a series of seven patients with onset of moderate (two patients) or severe (five patients) POPH before LTx, of whom six were treated with oral vasodilator therapy for POPH. Although previous studies recommend aggressive parenteral prostacyclin therapy (epoprostenol), we describe the opportunity to treat cases of severe POPH with an oral phosphodiesterase type 5 inhibitor (sildenafil) and/or an endothelin receptor antagonist (bosentan/ambrisentan) as a bridge to successful LTx in selected patients.

Defining an extended criteria donor lung: an empirical approach based on the Eurotransplant experience1

The aim of this study was to design and validate a lung donor score that reflects experts’ perceived risk of allograft failure. All lung donors reported to Eurotransplant from 1999 to 2007 [N = 6080] were used to create a lung donor score. Based on observed discard rates and using multivariate regression, points were assigned for six preprocurement donor variables. Donors reported in 2008 were used to validate the score [N = 751]. All the six factors significantly predicted discard; as an example, the following donor with points: age 55–59 years: 2; compromised history: 4; smoking: 2; shadow on chest X‐ray: 2; purulent secretion during bronchoscopy: 2; and Pao2/Fio2 ratio below 300 mmHg: 3. Discard rates for donors with a lung donor score of 6 points (class 1) was 18%, while 36% and 54% of the donors with a score of 7–8 (class 2) and 9 +  (class 3) were discarded (P < 0.001), respectively. In addition, the donor lung score was significantly associated with 1‐year survival: class 1: 91%; class 2: 80%; and class 3: 72% (P = 0.017). The lung donor score accurately reflects the likelihood of organ acceptance and predicts patient mortality, and its application at time of donor reporting may facilitate donor risk assessment and patient selection.

Right Ventricular Function in Patients With Eisenmenger Syndrome

To evaluate (1) whether right ventricular (RV) dysfunction, evaluated using tricuspid annular plane systolic excursion (TAPSE) is associated with a worse outcome in patients with the Eisenmenger syndrome, (2) which variables are related to RV dysfunction, and (3) whether differences exist among simple pretricuspid, simple post-tricuspid, and combined shunt lesions. Patients with Eisenmenger syndrome, aged >18 years, who underwent echocardiography, were selected from the Belgian Eisenmenger registry and prospectively followed up using a Web-based registry. Cox regression analysis was performed to evaluate the relation to outcomes, defined as all-cause mortality, transplantation, and hospitalization for cardiopulmonary causes. Comparative and bivariate analysis was performed, where applicable. A total of 58 patients (mean age 35.1 ± 13.2 years, 32.8% men) were included. During a mean follow-up of 3.2 years, 22 patients (37.9%) reached the predefined end point. Only TAPSE (hazard ratio 0.820, 95% confidence interval 0.708 to 0.950; p = 0.008) was related to the adverse outcomes on multivariate analysis. Patients with pretricuspid shunt lesions were older (p <0.0001) had greater left (p <0.0001) and right atrial (p <0.0001) dimensions, greater RV dimensions (p = 0.002), and more tricuspid regurgitation (p = 0.012) compared to patients with post-tricuspid lesions. Lower TAPSE was related to the presence of pulmonary artery thrombosis (R = -0.378; p = 0.006). In conclusion, in patients with Eisenmenger syndrome, RV dysfunction, evaluated using TAPSE, is related to worse outcomes. Patients with Eisenmenger syndrome with pretricuspid shunt lesions were older and had greater left atrial, right atrial, and RV dimensions compared to patients with post-tricuspid lesions, indicating a difference in the RV response. Lower TAPSE was associated with the presence of pulmonary artery thrombosis.